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An EGFR targeting nanoparticle self assembled from a thermoresponsive polymer

2014; Wiley; Volume: 90; Issue: 7 Linguagem: Inglês

10.1002/jctb.4509

1097-4660

Stephen Goodall, Christopher B. Howard, Martina L. Jones, Trent P. Munro, Zhongfan Jia, Michael J. Monteiro, Stephen M. Mahler,

Protein purification and stability

Abstract BACKGROUND Decorating nanoparticles with proteins, antibodies and antibody fragments allows highly specific targeting to selected cells for improved delivery of therapeutics and diagnostics. A range of particles have previously been trialled in drug delivery including liposomes, dendrimers, hydrogels and inorganic particles. Polymer nanoparticles can be rationally designed and self‐assembled with control over particle size, morphology, charge and shape, allowing for optimization of drug delivery. However, post‐functionalization of particles with antibodies or proteins can influence the self‐assembly process and creates challenges in maintaining bioactivity. RESULTS An EGFR ‐targeting scFv antibody fragment has been integrated as a hydrophilic moiety, and through self‐assembly driven by a thermoresponsive polymer, formed antibody‐targeted polymeric nanoparticles (immunoparticles) of approximately 320 nm in diameter. The binding of the scFv to native EGFR on MDA MB 468 cells and to recombinant EGFR was determined using flow cytometry and surface plasmon resonance respectively. Conjugation of the scFv to the thermoresponsive polymer did not compromise the binding to EGFR . Furthermore, cross‐linking the scFv with glutaraldehyde to stabilize the immunoparticle did not impact the binding of the particle to EGFR . CONCLUSION The temperature‐induced self‐assembly of immunoparticles from antibody‐conjugated polymers provides a novel method to prepare targeted nanoparticles. This methodology further provides a rapid and versatile way to build immunoparticles with multi‐targeting capability by combining different types of scFv‐PNIPAM conjugates targeting different receptors. © 2014 Society of Chemical Industry